impact of prenatal diagnosis in Egyptian families with Duchenne muscular dystrophy

Duchenne Muscular Dystrophy [DMD] is one of the most common lethal X-linked recessive genetic muscle disorders. It is caused by various mutations in the dystrophin gene. Due to the lack of efficient rehabilitation and treatment, prenatal diagnosis and proper genetic counseling of families with DMD are of great importance. This study aimed to evaluate an Egyptian prenatal molecular experience considering the impact of molecular information, the availability of prenatal diagnosis, and the changing attitude and choices of the Egyptian families with DMD. The study characterized the deletion patterns in 85 Egyptian patients with DMD and 32 fetuses from 27 mothers with previous history of DMD deletion mutations. Multiplex PCR amplification of 18 exons covering the two hotspots within the dystrophin gene was pursued to detect deletions in the probands. Detection of deletions in the fetal DNA was performed by using the targeted multiplex containing the deleted exons. Forty-six out of eighty-five probands [55%] had deletion mutations. Twenty-four out of the forty-six [52%] probands had multiple exons deletion and twenty-two [48%] showed single exon deletion. Out of the thirty-two amniotic fetal samples, fourteen fetuses inherited the same deletions present in the index cases while eighteen were normal. An emerging awareness of genetic information was observed and an apparent higher number of mothers seeking prenatal diagnosis was noticed. A change of attitude in favor of choosing the decision of abortion was apparent. Molecular diagnosis is an important tool for preventive medicine. It has an obvious impact on prenatal diagnosis and accurate genetic counseling. It also seems to have an impact on the attitude and choices of families in particular and society in general

Molecular characterization of 21 hydroxylase deficiency congenital adrenal hyperplasia in Egyptian children: a pilot study

Defective steroid synthesis due to derangements of 21-hydroxylase gene [CYP21] constitutes the most frequent cause of congenital adrenal hyperplasia [CAH] and is one of the most frequent inborn errors of metabolism world wide. The molecular basis of CYP21 mutations is complicated. During meiosis gene conversion occurs and transfers deleterious point mutations from the inactive [CYP21P] to the corresponding sequence of the CYP21 gene causing either complete or partial inactivation of 21-hydroxylase activity. Allele specific polymerase chain reaction [ASPCR] was used for the detection of the 4 most common mutations in CYP21 gene: Intron 2 splice mutations [IVS2-13], 8bp deletion in exon 3 [del-8bp], I172N mutation in exon 4 and V281L mutation in exon 7, in 11 salt wasting SW-CAH Egyptian infants. In the examined 22 alleles, 2 alleles were carrying del-8bp, 3 were carrying IVS2-13 mutation, 4 with I172N, 4 with V281L. In the present study the percentage of undetectable mutations was 50%. The wide range of genetic mutations reported for CYP21 gene reconfirm the marked heterogeneity of the disorder among Egyptian and calls for more extensive molecular work

High prevalence of the Cyp21 V281L mutation in Egyptian lean women with polycystic ovaries and infertility

This study included 42 females [in the childbearing period] were who presented with irregular menstruation and infertility and had ultrasonographic findings of polycystic ovaries. Clinical evaluation was done including body mass index [BMI] calculation. Measurement of morning fasting blood levels of testosterone, 17 alpha hydroxyprogesterone [OHP], follicle stimulating hormone, luteinizing hormone, glucose and insulin was done on the 5th post-menstrual day. Insulin resistance [IR] was estimated using the homeostasis model assessment [HOMA] method. Genomic DNA was extracted from peripheral blood leukocytes and allele specific polymerase chain reaction was used to screen for the exon 7 V281L missense mutation. In conclusion, NC-21OHD due to V281L mutation has been shown to be a major underlying etiology among Egyptians presenting with PCO and infertility. This calls for the importance of screening for this adrenal disorder among this patient group in order to institute proper therapeutic strategies

Benign X-linked Becker muscular dystrophy among Egyptian patients

This study included 30 male patients, their age ranged from 9 to 42 years. Becker muscle dystrophy [BMD] diagnosis was established in all patients on the base of the clinical and neurological assessment as well as the myopathic pattern of electromyography and the marked elevation of serum creatine phosphokinase enzyme. The diagnosis was confirmed by DNA analysis of dystrophin gene. Muscle biopsy studies were done using histochemical and enzyme histochemistry techniques as well as immunohistochemical study of dystrophin protein. BMD patients spanned a wide range of disease severity. DNA analysis revealed that either single or multiple deletion mutations within the dystrophin gene in all patients confirmed the diagnosis of BMD. Muscle biopsy studies showed changes specific for BMD as well as an abnormal expression of dystrophin protein